Genetic Risk Factors for Hypertrophic Scar Development

Abstract

Objective Hypertrophic scars (HTS) occur in 30–72% patients following thermal injury. Risk factors include skin color, female gender, young age, burn site, & burn severity. Recent correlations between genetic variations and clinical conditions suggest that single nucleotide polymorphisms (SNPs) may be associated with HTS formation. We hypothesized that a SNP in the p27kip1 gene (rs36228499) previously associated with decreased restenosis after coronary stenting would be associated with lower Vancouver scar scale (VSS) measurements and decreased itching. Methods Patient & injury characteristics were collected from adults with thermal burns. VSS scores were calculated at 4–9 months following injury. Genotyping was performed using real time PCR. Logistic regression was used to determine risk factors for hypertrophic scar as measured by a VSS score >7. Results 300 subjects had a median age of 39 years (range 18–91); 69% were male & median burn size was 7% TBSA (range 0.25–80). Consistent with literature, the p27kip1 variant SNP had an allele frequency of 40%, but was not associated with reduced HTS formation or lower itch scores in any genetic model. HTS formation was associated with American Indian/Alaskan Native race (OR, 12.2; P=0.02), facial burns (OR, 9.4; P=0.04), and burn size ≥20% TBSA (OR, 1.99; P=0.03). Conclusions Whereas the p27kip1 SNP may protect against vascular fibroproliferation, the effect cannot be generalized to cutaneous scars. Our study suggests that American Indian/Alaskan Native race, facial burns, and higher %TBSA are independent risk factors for HTS. The American Indian/Alaskan Native association suggests that there are potentially yet-to-be-identified genetic variants.

A prospective study of time to healing and hypertrophic scarring in paediatric burns: every day counts

“…Several published studies consist of retrospective case note reviews where any documentation of a scar which is red or raised constitutes a diagnosis of HTS [5, 9]. Other studies use the height of the scar alone [10, 11] or VSS [12] to diagnose HTS. In addition, some papers consider hypertrophic scars alone whereas others combine HTS with contracted or keloid scars to give an overview of pathological scarring [13].…”

“…Gangemi et al showed that female sex, younger age, burn sites on the neck or upper limbs, multiple surgical procedures and meshed skin grafts were all independent risk factors for developing pathological post burn scarring [13]. Hypertrophic burn scars are more common in non-white patient populations [4, 9, 12], and this has also been shown to be true for other types of surgical wounds [15]. Berchialla used these identified risk factors to predict risk of hypertrophic scarring using Bayesian networks [16].…”

“…Thompson et al showed that HTS was more common in American Indian/Alaskan Native race (and also in TBSA >20% and facial burns) but were unable to identify the genetic variant responsible for this finding [12]. A recent study from the UK has failed to show a clear link between skin type and incidence of HTS, but this study included small numbers of non-white patients; just 18 of 181 patients had a Fitzpatrick skin type of 4 or above [11].…”

Mesenchymal stem cells for sweat gland regeneration after burns: From possibility to reality

“…Sweat gland is a kind of important appendage of the skin, which plays some key roles in homeostasis maintenance and body temperature regulation. The skin of patients with an extensive deep burn is repaired by a hypertrophic scar [2] without regeneration of sweat glands, and therefore loses the function of perspiration. Burns survivors feel the heat very much and have to rest at home in summer, which affects their quality of life.…”

Abdominal scar characteristics as a predictor of cervical stenosis after abdominal radical trachelectomy

“…The higher the sum of the scores, the more marked or abnormal the scarring [12]. Thompson et al used a VSS score of > 7 as a way of identifying hypertrophic scars [14]. In this study, we discovered a relationship between the VSS score and the presence of cervical stenosis after ART.…”